Valtrex

VALTREX A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P ...

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VALTREX A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Valtrex: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84181-0 1. Valtrex-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Valtrex. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON VALTREX ................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Valtrex .......................................................................................... 4 E-Journals: PubMed Central ......................................................................................................... 5 The National Library of Medicine: PubMed .................................................................................. 5 CHAPTER 2. NUTRITION AND VALTREX ......................................................................................... 19 Overview...................................................................................................................................... 19 Finding Nutrition Studies on Valtrex ......................................................................................... 19 Federal Resources on Nutrition ................................................................................................... 20 Additional Web Resources ........................................................................................................... 20 CHAPTER 3. CLINICAL TRIALS AND VALTREX ................................................................................ 21 Overview...................................................................................................................................... 21 Recent Trials on Valtrex .............................................................................................................. 21 Keeping Current on Clinical Trials ............................................................................................. 26 CHAPTER 4. PATENTS ON VALTREX ................................................................................................ 29 Overview...................................................................................................................................... 29 Patent Applications on Valtrex.................................................................................................... 29 Keeping Current .......................................................................................................................... 31 CHAPTER 5. PERIODICALS AND NEWS ON VALTREX ...................................................................... 33 Overview...................................................................................................................................... 33 News Services and Press Releases................................................................................................ 33 Academic Periodicals covering Valtrex........................................................................................ 35 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 37 Overview...................................................................................................................................... 37 U.S. Pharmacopeia....................................................................................................................... 37 Commercial Databases ................................................................................................................. 38 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 41 Overview...................................................................................................................................... 41 NIH Guidelines............................................................................................................................ 41 NIH Databases............................................................................................................................. 43 Other Commercial Databases....................................................................................................... 45 APPENDIX B. PATIENT RESOURCES ................................................................................................. 47 Overview...................................................................................................................................... 47 Patient Guideline Sources............................................................................................................ 47 Finding Associations.................................................................................................................... 49 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 51 Overview...................................................................................................................................... 51 Preparation................................................................................................................................... 51 Finding a Local Medical Library.................................................................................................. 51 Medical Libraries in the U.S. and Canada ................................................................................... 51 ONLINE GLOSSARIES.................................................................................................................. 57 Online Dictionary Directories ..................................................................................................... 57 VALTREX DICTIONARY .............................................................................................................. 59 INDEX ................................................................................................................................................ 77

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Valtrex is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about Valtrex, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to Valtrex, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on Valtrex. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to Valtrex, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on Valtrex. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON VALTREX Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Valtrex.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Valtrex, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “Valtrex” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Herpes Simplex Virus: Clinical Presentation and Treatment Source: Dentistry Today. 20(5): 65-67. May 2001. Contact: Available from Dentistry Today Inc. 26 Park Street, Montclair, NJ 07042. (973) 783-3935. Summary: This continuing education article familiarizes dental practitioners with the clinical presentation and treatment of herpes simplex virus (HSV). Topics include the virus and its pathogenesis, transmission, diagnosis, clinical presentation (symptoms), treatment of orolabial (mouth and lips) HSV infections, and the pharmacological (drug) treatment of orolabial HSV infections. The author stresses that practitioners should be aware of the 'asymptomatic virus shedding' phenomenon, in which a patient with HSV who does not have clinical symptoms is contagious approximately 4 percent of the time.

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Treatment with acyclovir (Zovirax) and valacyclovir (Valtrex) is common, however, neither product is labeled for use in orolabial herpes. Other treatment strategies include counseling the patient to determine infection triggers, modify lifestyle to reduce those triggers, wear a wide brimmed hat and use a sunscreen with greater than SPF 30, and consider the use of drug agents during the prodrome (preblister) stage. A brief posttest for continuing education credits is appended to the article. 2 tables. 13 references.

Federally Funded Research on Valtrex The U.S. Government supports a variety of research studies relating to Valtrex. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Valtrex. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore Valtrex. The following is typical of the type of information found when searching the CRISP database for Valtrex: •

Project Title: INVESTIGATION OF VALTREX IN MULTIPLE SCLEROSIS Principal Investigator & Institution: Friedman, Jacqueline; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001 Summary: Multiple sclerosis (MS) is a disease which significantly affects areas of the central nervous system required for normal neurological functioning. Pathological studies of patients have suggested a viral etiology for this disease, based on similarities to known viral illnesses and the pathological changes observed. Epidemiological studies also support the hypothesis of a viral cause of MS with reported outbreaks of the disease in areas such as the Faeroe Islands. We now believe that our laboratory at the Rockefeller University, as well as other research labs, have sufficient preliminary evidence to warrant a clinical trial in MS using an anti-herpes antibiotic, Valtrex, to determine if the ravages of this disease can be controlled. Specifically, we have demonstrated that the Human herpes type -6 (HHV-6) virus can be detected by immunological methods in post mortem brain specimens of MS patients (oligodendrocyte glial cells), but not in brain specimens from decedents with other diseases. In addition HHV-6 DNA has been detected in MS brain tissue by the PCR technique, but not in controls. Finally, MS patients have a high serum antibody response to the Herpes-6 virus. Valtrex is a drug inhibitory to the HHV-6 virus with a good safety profile and is FDA approved. The general plan of study is to enroll 60 patients into a two-year trial with half randomly assigned to receive the drug and the other half a

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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placebo. The patients will be evaluated over the trial period by two neurologists, one of whom will not know which treatment the patients have been assigned, to assess disease progression and to evaluate disability, as measured in disability rating scales. In addition the frequency of attacks will be monitored and serial brain M.R.I. scans will be obtained to determine the number of brain lesions. Blood and spinal fluid will be periodically drawn to determine the immune response to the HHV-6 virus in the Valtrex study patients and in patients not in the drug trial, but followed at Rockefeller under the protocol "Immunological Studies in MS." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Valtrex” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for Valtrex in the PubMed Central database: •

High-Dose, Short-Duration, Early Valacyclovir Therapy for Episodic Treatment of Cold Sores: Results of Two Randomized, Placebo-Controlled, Multicenter Studies. by Spruance SL, Jones TM, Blatter MM, Vargas-Cortes M, Barber J, Hill J, Goldstein D, Schultz M.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149313

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Valtrex, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Valtrex” (or synonyms) 3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Valtrex (hyperlinks lead to article summaries): •

A double-blind, randomized study assessing the equivalence of valacyclovir 1000 mg once daily versus 500 mg twice daily in the episodic treatment of recurrent genital herpes. Genival Study Group. Author(s): Saiag P, Praindhui D, Chastang C. Source: The Journal of Antimicrobial Chemotherapy. 1999 October; 44(4): 525-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10588314&dopt=Abstract

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A neutropenia suggesting an interaction between valacyclovir and mycophenolate mofetil. Author(s): Royer B, Zanetta G, Berard M, Davani S, Tanter Y, Rifle G, Kantelip JP. Source: Clinical Transplantation. 2003 April; 17(2): 158-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709084&dopt=Abstract

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A randomized prospective controlled trial of oral ganciclovir versus oral valacyclovir for prophylaxis of cytomegalovirus disease after renal transplantation. Author(s): Reischig T, Opatrny K Jr, Bouda M, Treska V, Jindra P, Svecova M. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2002 December; 15(12): 615-22. Epub 2002 November 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478408&dopt=Abstract

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A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. The Valaciclovir International Study Group. Author(s): Tyring SK, Douglas JM Jr, Corey L, Spruance SL, Esmann J. Source: Archives of Dermatology. 1998 February; 134(2): 185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9487210&dopt=Abstract

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A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Author(s): Lerner AM, Beqaj SH, Deeter RG, Dworkin HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O'Neill W. Source: Drugs Today (Barc). 2002 August; 38(8): 549-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582420&dopt=Abstract

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Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Author(s): Lycke J, Malmestrom C, Stahle L. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2438-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878501&dopt=Abstract

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An investigation of the steady-state pharmacokinetics of oral valacyclovir in immunocompromised children. Author(s): Nadal D, Leverger G, Sokal EM, Floret D, Perel Y, Leibundgut K, Weller S. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S123-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353197&dopt=Abstract

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Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Author(s): Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ. Source: Archives of Family Medicine. 2000 September-October; 9(9): 863-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11031393&dopt=Abstract

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Aseptic meningitis related to valacyclovir. Author(s): Fobelo MJ, Corzo Delgado JE, Romero Alonso A, Gomez-Bellver MJ. Source: The Annals of Pharmacotherapy. 2001 January; 35(1): 128-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197578&dopt=Abstract

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Choreiform movements in dialysis patient taking valacyclovir and famciclovir. Author(s): Maru MC, Fialkow RZ, Haria DM. Source: Southern Medical Journal. 2001 June; 94(6): 655. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440337&dopt=Abstract

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Clinical utility of oral valacyclovir compared with oral acyclovir for the prevention of herpes simplex virus mucositis following autologous bone marrow transplantation or stem cell rescue therapy. Author(s): Eisen D, Essell J, Broun ER, Sigmund D, DeVoe M. Source: Bone Marrow Transplantation. 2003 January; 31(1): 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621507&dopt=Abstract

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Comparative bioavailability of acyclovir from oral valacyclovir and acyclovir in patients treated for recurrent genital herpes simplex virus infection. Author(s): Bras AP, Sitar DS, Aoki FY. Source: Can J Clin Pharmacol. 2001 Winter; 8(4): 207-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743593&dopt=Abstract

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Comparative study of prophylactic oral ganciclovir and valacyclovir in high-risk kidney transplant recipients. Author(s): Yango A, Morrissey P, Zanabli A, Beaulieu J, Shemin D, Dworkin L, Monaco A, Gohh R. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 April; 18(4): 809-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637653&dopt=Abstract

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Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir. Author(s): Balimane PV, Tamai I, Guo A, Nakanishi T, Kitada H, Leibach FH, Tsuji A, Sinko PJ. Source: Biochemical and Biophysical Research Communications. 1998 September 18; 250(2): 246-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9753615&dopt=Abstract

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Effect of ionization on the variable uptake of valacyclovir via the human intestinal peptide transporter (hPepT1) in CHO cells. Author(s): Balimane P, Sinko P. Source: Biopharmaceutics & Drug Disposition. 2000 July; 21(5): 165-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180195&dopt=Abstract

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Epstein-Barr virus replication in oral hairy leukoplakia: response, persistence, and resistance to treatment with valacyclovir. Author(s): Walling DM, Flaitz CM, Nichols CM. Source: The Journal of Infectious Diseases. 2003 September 15; 188(6): 883-90. Epub 2003 Sep 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964120&dopt=Abstract

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Famciclovir and valacyclovir. Author(s): Dawson LJ, Morgan DK. Source: American Family Physician. 1998 March 1; 57(5): 947. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9518945&dopt=Abstract

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Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. Author(s): Landowski CP, Sun D, Foster DR, Menon SS, Barnett JL, Welage LS, Ramachandran C, Amidon GL. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 August; 306(2): 778-86. Epub 2003 May 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750437&dopt=Abstract

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Generic acyclovir vs. famciclovir and valacyclovir. Author(s): Grose C, Wiedeman J. Source: The Pediatric Infectious Disease Journal. 1997 September; 16(9): 838-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9306476&dopt=Abstract

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High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies. Author(s): Spruance SL, Jones TM, Blatter MM, Vargas-Cortes M, Barber J, Hill J, Goldstein D, Schultz M. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 1072-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604544&dopt=Abstract

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Identification of a human valacyclovirase: biphenyl hydrolase-like protein as valacyclovir hydrolase. Author(s): Kim I, Chu XY, Kim S, Provoda CJ, Lee KD, Amidon GL. Source: The Journal of Biological Chemistry. 2003 July 11; 278(28): 25348-56. Epub 2003 May 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732646&dopt=Abstract

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Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line. Author(s): Guo A, Hu P, Balimane PV, Leibach FH, Sinko PJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 April; 289(1): 448-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10087037&dopt=Abstract

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Intra- and interindividual variabilities of valacyclovir oral bioavailability and effect of coadministration of an hPEPT1 inhibitor. Author(s): Phan DD, Chin-Hong P, Lin ET, Anderle P, Sadee W, Guglielmo BJ. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2351-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821497&dopt=Abstract

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Neurotoxicity caused by valacyclovir in a patient on hemodialysis. Author(s): Linssen-Schuurmans CD, van Kan EJ, Feith GW, Uges DR. Source: Therapeutic Drug Monitoring. 1998 August; 20(4): 385-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9712461&dopt=Abstract

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Neurotoxicity of valacyclovir in peritoneal dialysis: a pharmacokinetic study. Author(s): Izzedine H, Mercadal L, Aymard G, Launay-Vacher V, Martinez V, Issad B, Deray G. Source: American Journal of Nephrology. 2001 March-April; 21(2): 162-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359026&dopt=Abstract

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New drugs--reports of new drugs recently approved by the FDA. Valacyclovir. Author(s): Shinkai I, Ohta Y. Source: Bioorganic & Medicinal Chemistry. 1996 January; 4(1): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8689229&dopt=Abstract

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Once-daily valacyclovir hydrochloride for suppression of recurrent genital herpes. Author(s): Baker DA, Blythe JG, Miller JM. Source: Obstetrics and Gynecology. 1999 July; 94(1): 103-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389727&dopt=Abstract

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Oral valacyclovir in the treatment of acute retinal necrosis syndrome. Author(s): Aslanides IM, De Souza S, Wong DT, Giavedoni LR, Altomare F, Detorakis ET, Kymionis GD, Pallikaris IG. Source: Retina (Philadelphia, Pa.). 2002 June; 22(3): 352-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055471&dopt=Abstract

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Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus infections in autologous stem cell transplant recipients. Author(s): Liesveld JL, Abboud CN, Ifthikharuddin JJ, Lancet JE, Wedow LA, Oliva J, Stamm CG, Nichols D. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2002; 8(12): 662-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523578&dopt=Abstract

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Outcome of treatment with valacyclovir and prednisone in patients with Bell's palsy. Author(s): Axelsson S, Lindberg S, Stjernquist-Desatnik A. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 March; 112(3): 197201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656408&dopt=Abstract

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Patients' preference of valacyclovir once-daily suppressive therapy versus twice-daily episodic therapy for recurrent genital herpes: a randomized study. Author(s): Romanowski B, Marina RB, Roberts JN; Valtrex HS230017 Study Group. Source: Sexually Transmitted Diseases. 2003 March; 30(3): 226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616141&dopt=Abstract

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Pediatric uses of valacyclovir, penciclovir and famciclovir. Author(s): Dekker CL, Prober CG. Source: The Pediatric Infectious Disease Journal. 2001 November; 20(11): 1079-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734715&dopt=Abstract

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Pharmacokinetics of acyclovir in immunocompromized children with leukopenia and mucositis after chemotherapy: can intravenous acyclovir be substituted by oral valacyclovir? Author(s): Eksborg S, Pal N, Kalin M, Palm C, Soderhall S. Source: Medical and Pediatric Oncology. 2002 April; 38(4): 240-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920787&dopt=Abstract

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Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy. Author(s): Kimberlin DF, Weller S, Whitley RJ, Andrews WW, Hauth JC, Lakeman F, Miller G. Source: American Journal of Obstetrics and Gynecology. 1998 October; 179(4): 846-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9790357&dopt=Abstract

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Pharmacology of new antiherpes agents: famciclovir and valacyclovir. Author(s): Stein GE. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 1997 March-April; Ns37(2): 157-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9069689&dopt=Abstract

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Quantitative effects of valacyclovir on the replication of cytomegalovirus (CMV) in persons with advanced human immunodeficiency virus disease: baseline CMV load dictates time to disease and survival. The AIDS Clinical Trials Group 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group. Author(s): Emery VC, Sabin C, Feinberg JE, Grywacz M, Knight S, Griffiths PD. Source: The Journal of Infectious Diseases. 1999 September; 180(3): 695-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10438356&dopt=Abstract

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Randomized comparison of oral valacyclovir and intravenous ganciclovir for prevention of cytomegalovirus disease after allogeneic bone marrow transplantation. Author(s): Winston DJ, Yeager AM, Chandrasekar PH, Snydman DR, Petersen FB, Territo MC; Valacyclovir Cytomegalovirus Study Group. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 March 15; 36(6): 749-58. Epub 2003 Mar 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627359&dopt=Abstract

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Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants. Author(s): Ljungman P, de La Camara R, Milpied N, Volin L, Russell CA, Crisp A, Webster A; Valacyclovir International Bone Marrow Transplant Study Group. Source: Blood. 2002 April 15; 99(8): 3050-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929799&dopt=Abstract

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Recurrent erythema multiforme unresponsive to acyclovir prophylaxis and responsive to valacyclovir continuous therapy. Author(s): Kerob D, Assier-Bonnet H, Esnault-Gelly P, Blanc F, Saiag P. Source: Archives of Dermatology. 1998 July; 134(7): 876-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9681359&dopt=Abstract

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Successful use of oral valacyclovir in post-transplant cytomegalovirus infection in renal allograft recipients. Author(s): Himmelmann-Jud B, Wuthrich RP, Weinreich T, Binswanger U. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1998 May; 13(5): 1326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9623588&dopt=Abstract

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Synthesis of analogs of L-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells. Author(s): Friedrichsen GM, Chen W, Begtrup M, Lee CP, Smith PL, Borchardt RT. Source: European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences. 2002 July; 16(1-2): 1-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113886&dopt=Abstract

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The economic value of valacyclovir prophylaxis in transplantation. Author(s): Squifflet JP, Legendre C. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S116-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353196&dopt=Abstract

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The effectiveness of valacyclovir in preventing reactivation of herpes gladiatorum in wrestlers. Author(s): Anderson BJ. Source: Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine. 1999 April; 9(2): 86-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10442623&dopt=Abstract

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The renal safety of high doses of valacyclovir for prevention of cytomegalovirus infection after renal transplantation. Author(s): Le Meur Y, Mons S, Moesch C, Leroux-Robert C. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 March; 15(3): 442. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10692544&dopt=Abstract

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Thymidine kinase (TK) gene therapy of solid tumors: valacyclovir facilitates outpatient treatment. Author(s): Hasenburg A, Tong XW, Rojas-Martinez A, Nyberg-Hoffman C, Kieback CC, Kaplan AL, Kaufman RH, Ramzy I, Aguilar-Cordova E, Kieback DG. Source: Anticancer Res. 1999 May-June; 19(3B): 2163-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10472325&dopt=Abstract

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Tomorrow's challenges for herpesvirus management: potential applications of valacyclovir. Author(s): Griffiths PD. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S131-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353198&dopt=Abstract

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Treatment of sudden sensorineural hearing loss with systemic steroids and valacyclovir. Author(s): Tucci DL, Farmer JC Jr, Kitch RD, Witsell DL. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 May; 23(3): 301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981385&dopt=Abstract

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Use of valacyclovir for herpes simplex virus-1 (HSV-1) prophylaxis after facial resurfacing: A randomized clinical trial of dosing regimens. Author(s): Gilbert S, McBurney E. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 January; 26(1): 50-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10632686&dopt=Abstract

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Valacyclovir and famciclovir therapy in herpes zoster. Author(s): Jubelt B. Source: Curr Neurol Neurosci Rep. 2002 November; 2(6): 477-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359099&dopt=Abstract

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Valacyclovir for episodic treatment of genital herpes: a shorter 3-day treatment course compared with 5-day treatment. Author(s): Leone PA, Trottier S, Miller JM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 April 1; 34(7): 958-62. Epub 2002 February 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880962&dopt=Abstract

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Valacyclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years' experience with acyclovir. Author(s): Tyring SK, Baker D, Snowden W. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S40-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353186&dopt=Abstract

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Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind, placebocontrolled studies. Author(s): Baker D, Eisen D. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 March; 71(3): 239-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661753&dopt=Abstract

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Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. Author(s): Lowance D, Neumayer HH, Legendre CM, Squifflet JP, Kovarik J, Brennan PJ, Norman D, Mendez R, Keating MR, Coggon GL, Crisp A, Lee IC. Source: The New England Journal of Medicine. 1999 May 13; 340(19): 1462-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10320384&dopt=Abstract

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Valacyclovir for the prevention of cytomegalovirus infection after allogeneic stem cell transplantation: a single institution retrospective cohort analysis. Author(s): Vusirikala M, Wolff SN, Stein RS, Brandt SJ, Morgan DS, Greer JP, Schuening FG, Dummer JS, Goodman SA. Source: Bone Marrow Transplantation. 2001 August; 28(3): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535994&dopt=Abstract

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Valacyclovir for the prevention of cytomegalovirus infection after kidney transplantation is associated with macrocytosis. Author(s): Baud J, El Haggan W, Naguib D, Troussard X, Hurault de Ligny B. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 January; 3(1): 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492719&dopt=Abstract

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Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects. Author(s): DeJesus E, Wald A, Warren T, Schacker TW, Trottier S, Shahmanesh M, Hill JL, Brennan CA; Valacyclovir International HSV Study Group. Source: The Journal of Infectious Diseases. 2003 October 1; 188(7): 1009-16. Epub 2003 September 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513421&dopt=Abstract

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Valacyclovir HCl (Valtrex): an acyclovir prodrug with improved pharmacokinetics and better efficacy for treatment of zoster. Author(s): Smiley ML, Murray A, de Miranda P. Source: Advances in Experimental Medicine and Biology. 1996; 394: 33-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8815698&dopt=Abstract

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Valacyclovir hydrochloride therapy and thrombotic thrombocytopenic purpura in an HIV-infected patient. Author(s): Rivaud E, Massiani MA, Vincent F, Azoulay E, Coudrec LJ. Source: Archives of Internal Medicine. 2000 June 12; 160(11): 1705-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10847274&dopt=Abstract

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Valacyclovir in the treatment of facial herpes simplex virus infection. Author(s): Laiskonis A, Thune T, Neldam S, Hiltunen-Back E. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S66-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353189&dopt=Abstract

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Valacyclovir in the treatment of genital herpes and herpes zoster. Author(s): Baker DA. Source: Expert Opinion on Pharmacotherapy. 2002 January; 3(1): 51-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772333&dopt=Abstract

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Valacyclovir neurotoxicity in a patient with end-stage renal disease treated with continuous ambulatory peritoneal dialysis. Author(s): Okada T, Nakao T, Matsumoto H, Nagaoka Y, Iwasawa H, Nanri K, Yamazaki T. Source: Clinical Nephrology. 2002 August; 58(2): 168-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227692&dopt=Abstract

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Valacyclovir prevention of cytomegalovirus reactivation after heart transplantation: a randomized trial. Author(s): Egan JJ, Carroll KB, Yonan N, Woodcock A, Crisp A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 April; 21(4): 460-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927223&dopt=Abstract

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Valacyclovir prophylaxis for herpes simplex virus infection or infection recurrence following laser skin resurfacing. Author(s): Beeson WH, Rachel JD. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 April; 28(4): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966791&dopt=Abstract

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Valacyclovir prophylaxis for the prevention of Herpes simplex virus reactivation in recipients of progenitor cells transplantation. Author(s): Dignani MC, Mykietiuk A, Michelet M, Intile D, Mammana L, Desmery P, Milone G, Pavlovsky S. Source: Bone Marrow Transplantation. 2002 February; 29(3): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859400&dopt=Abstract

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Valacyclovir provides optimum acyclovir exposure for prevention of cytomegalovirus and related outcomes after organ transplantation. Author(s): Fiddian P, Sabin CA, Griffiths PD. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S110-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353195&dopt=Abstract

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Valacyclovir study stopped -- worse survival. Author(s): James JS. Source: Aids Treat News. 1995 February 17; (No 217): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11362306&dopt=Abstract

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Valacyclovir to prevent cytomegalovirus disease after renal transplantation. Author(s): Shapiro ME, Abrams JM. Source: The New England Journal of Medicine. 1999 September 16; 341(12): 921. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10498468&dopt=Abstract

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Valacyclovir versus acyclovir for HSV prophylaxisin neutropenic patients. Author(s): Warkentin DI, Epstein JB, Campbell LM, Yip JG, Cox VC, Ransier A, Barnett MJ, Marra F. Source: The Annals of Pharmacotherapy. 2002 October; 36(10): 1525-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243600&dopt=Abstract

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Valacyclovir. Author(s): Acosta EP, Fletcher CV. Source: The Annals of Pharmacotherapy. 1997 February; 31(2): 185-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9034421&dopt=Abstract

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Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy. Author(s): Beutner KR. Source: Antiviral Research. 1995 December; 28(4): 281-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8669888&dopt=Abstract

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Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Author(s): Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH. Source: Biochemical and Biophysical Research Communications. 1998 May 19; 246(2): 470-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9610386&dopt=Abstract

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CHAPTER 2. NUTRITION AND VALTREX Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Valtrex.

Finding Nutrition Studies on Valtrex The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Valtrex” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “Valtrex” (or a synonym): •

Valacyclovir (valtrex) for herpes labialis. Source: Anonymous Med-Lett-Drugs-Ther. 2002 November 11; 44(1143): 95-6 0025-732X

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. CLINICAL TRIALS AND VALTREX Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Valtrex.

Recent Trials on Valtrex The following is a list of recent trials dedicated to Valtrex.8 Further information on a trial is available at the Web site indicated. •

A Pharmacokinetic Study of Valacyclovir in Pediatric Oncology Patients Condition(s): Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): Baylor College of Medicine; Texas Children's Hospital Purpose - Excerpt: The purpose of this research is to study the pharmacology (how the body handles this drug) of valacyclovir in children receiving treatment for cancer. This study will last approximately 7 days. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042328

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Randomized Study of Two Doses of Oral Valacyclovir in Immunocompromised Patients With Uncomplicated Herpes Zoster Condition(s): Herpes Zoster; Immunologic Deficiency Syndromes Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); University of Texas

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These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: Objectives: I. Compare the efficacy and safety of two doses of oral valacyclovir in immunocompromised patients with uncomplicated herpes zoster. II. Compare quality of life, pain, and medical resource utilization in patients treated with these 2 regimens. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006131 •

Valacyclovir for longterm therapy of Herpes simplex encephalitis Condition(s): Encephalitis, Herpes Simplex Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if giving Valacyclovir (VACV) to patients with herpes simplex encephalitis (HSE) can increase the survival rates of these patients and reduce brain and nervous system damage. A sub-study will also be performed to look at the relationship between the level of herpes virus in the blood and "long-term" brain damage injury caused by the HSE infection. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031486

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Valacyclovir in Immunocompromised Children Condition(s): Shingles; Bone Marrow Transplantation Study Status: This study is currently recruiting patients. Sponsor(s): Baylor College of Medicine; Texas Children's Hospital Purpose - Excerpt: Shingles is an infection commonly seen in children with a weakened immune system (immunocompromised children). The immune system can be weakened as a result of medications that patients receive for cancer or other serious illness or as a result of a bone marrow transplantation. Shingles in children with a weakened immune system may spread throughout the body and in some instances may be life-threatening. Acyclovir is a medication that is routinely used to treat immunocompromised children with shingles in order to prevent further spread of their shingles and to help them heal faster. Acyclovir is also given to bone marrow transplant patients to prevent reactivation of HSV infection. Valacyclovir is a new drug that is metabolized (broken down in the body) to acyclovir. Valacyclovir is given by mouth and studies done in adults have shown it to be more effective than acyclovir given by mouth. The purpose of this study is to * study the pharmacology of this drug (how the body handles this drug), * determine if oral Valacyclovir can be safely given to children with shingles, and * determine the type of side effects that occur when oral Valacyclovir is given to immunocompromised children. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00059592 •

Valacyclovir in Preventing Cytomegalovirus Infection in Patients Who Are Undergoing Donor Stem Cell Transplantation Condition(s): Infection Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Antivirals such as valacyclovir act against viruses and may be effective in preventing cytomegalovirus. It is not yet known if valacyclovir is effective in preventing cytomegalovirus in patients undergoing stem cell transplantation. PURPOSE: Randomized phase III trial to determine the effectiveness of valacyclovir in preventing cytomegalovirus in patients who are undergoing donor stem cell transplantation. Phase(s): Phase III; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045292

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A Study of Valacyclovir as Treatment for Genital Herpes Simplex Virus in HIVInfected Patients Condition(s): Herpes Simplex; HIV Infections; Herpes Genitalis Study Status: This study is no longer recruiting patients. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: The purpose of this study is to see if valacyclovir (Valtrex) is a safe and effective treatment for ano-genital HSV infections (herpes simplex virus infections of the anus and external genitals) in HIV-infected patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005663

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Effects of Long-Term Treatment with Valaciclovir (Valtrex) on Epstein-Barr Virus Condition(s): Epstein Barr Virus Infection; Healthy Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the effects of long-term antiviral therapy with valaciclovir (Valtrex) on Epstein-Barr virus infection. This virus infects more than 95 percent of people in the United States. Most are infected in childhood, have no symptoms, and are unaware of their infection. People infected as adolescents or adults may develop infectious mononucleosis, which usually resolves completely. Once infected, most people shed the virus from their throat occasionally, and all carry the virus in their white blood cells for life. This study will determine whether the amount of virus in the blood declines or disappears with long-term valaciclovir treatment. Normal volunteers who are not taking any antiviral medicines and patients enrolled in NIH's

24

Valtrex

protocol no. 97-I-0168 (Evaluation of Valaciclovir for Prevention of Herpes Simplex Virus Transmission) or Glaxo-Wellcome protocol HS2AB 3009 at collaborating centers may be eligible for this study. Patients in the multi-center study must be about to start valaciclovir therapy for at least 1 year. All candidates must be 18 years of age or older. Study participants will be seen in clinic for about 1 hour every 3 months for a year. During these visits, they will provide information about the medicines they are taking, gargle twice with salt water and spit the fluid into a tube, and have blood drawn (no more than 8 teaspoons each visit). The blood and gargled fluid will be tested for the amount of Epstein-Barr virus and antibodies to the virus. (Blood samples will also be tested for HLA type in order to do immunologic studies in the laboratory. HLA is a marker of the immune system that is similar to blood-typing testing.) The results in people taking valaciclovir will be compared with those in people not taking the drug. People whose results show the virus has disappeared from the body will continue to be followed twice a year for 5 years with the blood and gargling tests to continue to look for evidence of virus. Also, people who develop symptoms resembling mononucleosis (e.g., enlarged lymph nodes with fever and sore throat) will be asked to have their blood tested for the virus. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005924 •

A Comparative Trial of Valacyclovir Hydrochloride ( 256U87 ) and Acyclovir for the Suppression of Anogenital Herpes Infections in HIV-Infected Patients Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: To determine the safety and efficacy of oral valacyclovir hydrochloride ( 256U87 ) compared to acyclovir in the treatment of recurrent anogenital herpes in HIV-infected patients with CD4 counts = or > 100 cells/mm3. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002084

•

A Study of Valacyclovir Hydrochloride in the Prevention of Life-Threatening Cytomegalovirus Disease in HIV-Infected Patients Condition(s): Cytomegalovirus Infections; HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Glaxo Wellcome Purpose - Excerpt: PRIMARY: To evaluate the efficacy of valacyclovir hydrochloride (BW 256U87) in the prevention of cytomegalovirus (CMV) end-organ disease in HIV/CMV co-infected patients with CD4+ lymphocytes < 100 cells/mm3. To assess the impact of BW 256U87, high-dose oral acyclovir and low-dose oral acyclovir on survival. SECONDARY: To evaluate the effect of BW 256U87 on quality of life, the safety of the drug administered concurrently with standard antiretroviral agents and other essential therapies for the treatment and prevention of opportunistic diseases, and the efficacy of

Clinical Trials 25

BW 256U87 in suppressing activation of other herpesviruses. To evaluate serologic and virologic risk factors for the development of CMV disease, including assessment of HIV activation, and the risk of developing drug-resistant CMV, HSV, and VZV. Gastrointestinal absorption of acyclovir is not high enough to prevent CMV disease in patients with advanced HIV disease, although there is evidence that high doses of the drug may extend survival. Valacyclovir, a prodrug that is rapidly converted to acyclovir after oral administration, has a higher absorption rate and may therefore provide inhibitory activity against CMV. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001038 •

A Study to Compare the Efficacy and Safety of Valacyclovir Hydrochloride ( 256U87 ) Versus Acyclovir in the Treatment of Recurrent Anogenital Herpes Infections in HIV Infected Patients Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: To evaluate the safety and efficacy of oral valacyclovir hydrochloride (256U87) vs. acyclovir in the treatment of recurrent anogenital herpes in HIV-infected patients (CD4 greater than or equal to 100). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002000

•

The Effect of Valacyclovir on the Detection of HIV from Genital Herpes Lesions in HIV-Infected Patients Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: The purpose of this study is to see if valacyclovir affects the detection of HIV in genital herpes lesions in HIV-infected patients. Valacyclovir is used to treat recurrent genital herpes. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002404

•

The Safety and Effectiveness of Valacyclovir HCl in the Treatment of Herpes Simplex or Varicella/Zoster Infections in HIV-1 Infected Children Condition(s): Herpes Simplex; HIV Infections; Chickenpox Study Status: This study is terminated.

26

Valtrex

Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Glaxo Wellcome Purpose - Excerpt: To obtain tolerance, safety, and pharmacokinetic data for oral valacyclovir hydrochloride ( 256U87 ) in HIV-1 infected children with herpes simplex virus infections ( cold sores ) and/or varicella / zoster virus infections ( chicken pox / shingles ). Varicella and zoster are common problems in HIV-infected children. It is believed that chronic oral therapy with acyclovir may result in subtherapeutic concentrations of acyclovir, resulting in resistance to that drug. Valacyclovir hydrochloride, which converts to acyclovir in the body, increases acyclovir bioavailability by 3-5 fold. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001054

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Valtrex” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

•

For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

•

For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

Clinical Trials 27

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

•

For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

29

CHAPTER 4. PATENTS ON VALTREX Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Valtrex” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Valtrex, we have not necessarily excluded non-medical patents in this bibliography.

Patent Applications on Valtrex As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Valtrex:

9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 10 This has been a common practice outside the United States prior to December 2000.

30

Valtrex

•

Crystalline forms of valacyclovir hydrochloride Inventor(s): Aronhime, Judith; (Rehovot, IL), Blasberger, Dina; (Raanana, IL), Dolitzky, Ben-Zion; (Petach Tiqva, IL), Etinger, Marina Yu; (Nesher, IL), Niddam-Hildesheim, Valerie; (Even-Yeouda, IL), Nisnevich, Gennady A.; (Haifa, IL), Pertsikov, Boris; (Nesher, IL), Tishin, Boris; (Haifa, IL), Wizel, Shlomit; (Petah Tiqva, IL), Yuzefovich, Michael; (Haifa, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030114470 Date filed: September 6, 2002 Abstract: Provided are novel polymorphs and pseudopolymorphs of valacyclovir hydrochloride and pharmaceutical compositions containing these. Also provided are methods for making the novel polymorphs and pseudopolymorphs, which include valacyclovir hydrochloride monohydrate and valacyclovir hydrochloride dihydrate. Excerpt(s): This application claims the benefit of the following U.S. Provisional Applications No. 60/317,850, filed Sep. 7, 2001; No. 60/342,273, filed Dec. 21, 2001; No. 60/386,505, filed Jun. 5, 2002; and No. 60/403,838, filed Aug. 14, 2002. The present invention relates to novel crystalline forms (polymorphs and pseudopolymorphs) of the antiviral compound valacyclovir hydrochloride, and methods for obtaining them. Valacyclovir is an L-valyl ester prodrug of acyclovir. Acyclovir is an acyclic analog of a natural nucleoside which has been found to have high anti-viral activity. Acyclovir is widely used in the treatment and prophylaxis of viral infections in humans, particularly infections caused by the herpes group of viruses. See Goodman and Gilman's, The Pharmacological Basis of Therapeutics 1193-1198 (9th ed. 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Synthesis and purification of valacyclovir Inventor(s): Blasberger, Dina; (Raanana, IL), Dolitzky, Ben Zion; (Petach-Tiqva, IL), Etinger, Marina Yu; (Nesher, IL), Nisnevich, Gennady A.; (Haifa, IL), Pertsikov, Boris; (Nesher, IL), Tishin, Boris; (Haifa, IL), Yudovich, Lev M.; (Haifa, IL), Yuzefovich, Michael; (Haifa, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030153757 Date filed: November 13, 2002 Abstract: The present invention relates to protected valacyclovir, N-tertbutoxycarbonyl-L-valine 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-y- l)methoxy] ethyl ester, and a method of making it. The present invention further relates to a method of making valacyclovir including the steps of coupling an amine protected valine selected from N-t-butoxycarbonyl valine and N-formyl valine with acyclovir using a coupling agent to form a protected valacyclovir, and deprotecting the protected valacyclovir to form valacyclovir or a pharmaceutically acceptable salt thereof. The present invention further relates to valacyclovir in pure form, a method of making pure valacyclovir, and to compositions containing pure valacyclovir. Excerpt(s): This application claims the benefit of U.S. provisional application Serial No. 60/332,802, filed Nov. 14, 2001, and U.S. provisional application Serial No. 60/342,273, filed Dec. 21, 2001, both of which are incorporated herein by reference. The present

Patents 31

invention relates to protected valacyclovir, N-tert-butoxycarbonyl-L-valine 2-[(2-amino1,6-dihydro-6-oxo-9H-purin-9-y- l)methoxy] ethyl ester, and a method of making it. The present also invention relates to a novel method of synthesis and purification of the antiviral compound valacyclovir hydrochloride. The present invention further relates to valacyclovir in pure form, a method of making pure valacyclovir, and to compositions containing pure valacyclovir. Acyclovir has been found to have high anti-viral activity and is widely used in the treatment and prophylaxis of viral infections in humans, particularly infections caused by the herpes group of viruses. See Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 1193-1198 (9th ed. 1996). Acyclovir, as its sodium salt, is commercially available under the brand name Zovirax.RTM. U.S. Pat. No. 4,199,574 discloses the treatment of viral infections with acyclovir. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with Valtrex, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “Valtrex” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on Valtrex. You can also use this procedure to view pending patent applications concerning Valtrex. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. PERIODICALS AND NEWS ON VALTREX Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Valtrex.

News Services and Press Releases One of the simplest ways of tracking press releases on Valtrex is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “Valtrex” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to Valtrex. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “Valtrex” (or synonyms). The following was recently listed in this archive for Valtrex: •

U.S. FDA OKs Glaxo's Valtrex to prevent herpes Source: Reuters Industry Breifing Date: August 29, 2003

•

U.S. FDA okays Glaxo's Valtrex to prevent herpes Source: Reuters Health eLine Date: August 29, 2003

34

Valtrex

•

Glaxo earns FDA nod to market Valtrex to HIV-infected individuals Source: Reuters Industry Breifing Date: April 02, 2003

•

Glaxo hit by fears for Valtrex, Imigran patents Source: Reuters Industry Breifing Date: February 06, 2003

•

Glaxo's Valtrex approved as one-day cold sore treatment Source: Reuters Industry Breifing Date: September 10, 2002

•

FDA okays shorter Valtrex treatment course for recurrent herpes outbreaks Source: Reuters Industry Breifing Date: July 17, 2001 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Valtrex” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Valtrex” (or synonyms). If you know the name of a company that is relevant to Valtrex, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the

Periodicals and News

35

company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Valtrex” (or synonyms).

Academic Periodicals covering Valtrex Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Valtrex. In addition to these sources, you can search for articles covering Valtrex that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 6. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Valtrex. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with Valtrex. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

38

Valtrex

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Valtrex: Valacyclovir •

Systemic - U.S. Brands: Valtrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202790.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

39

APPENDICES

41

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

These publications are typically written by one or more of the various NIH Institutes.

42

Valtrex

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

43

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

12 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Valtrex” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 289 0 349 24 0 662

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “Valtrex” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

47

APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Valtrex can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to Valtrex. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to Valtrex. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “Valtrex”:

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•

Other guides Encephalitis http://www.nlm.nih.gov/medlineplus/encephalitis.html Herpes Simplex http://www.nlm.nih.gov/medlineplus/herpessimplex.html Sexually Transmitted Diseases http://www.nlm.nih.gov/medlineplus/sexuallytransmitteddiseases.html Shingles http://www.nlm.nih.gov/medlineplus/shinglesherpeszoster.html Viral Infections http://www.nlm.nih.gov/medlineplus/viralinfections.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Valtrex. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Erythema Multiforme Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail: [email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have erythema multiforme (EM) with information on the etiology, symptoms, and treatment of this acute, self limiting, inflammatory skin eruption. EM appears in multiple forms, and because of this variation EM has been divided into the overlapping subgroups EM minor and StevensJohnson syndrome (SJS). EM minor is usually caused by the herpes virus. Additional causes are other bacterial or viral infections or reactions to medications. EM minor is characterized by a rash that may be accompanied by minor burning or itch. Round bulls eye target shaped rings are usually present on the palms. SJS causes a greater degree of damage than EM minor. SJS is characterized by large blood blisters accompanied by a red rash. A skin biopsy is needed to confirm the diagnosis. Treatment of EM begins with the identification and removal of the trigger factor if possible. EM minor usually needs

Patient Resources

49

no treatment because the lesions will resolve themselves within 2 to 4 weeks. Recurrent EM caused by the herpes virus can be prevented with a continuous low dose of Zovirax or Valtrex. SJS, if identified in the early stages, can be treated with intravenous Cytoxan, pooled gamma globulin, or oral cyclosporine. Oral steroids are useful in some cases. 2 figures. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Valtrex. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Valtrex. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Valtrex. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about Valtrex. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

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Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Valtrex” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “Valtrex”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “Valtrex” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Valtrex” (or a synonym) into the search box, and click “Submit Query.”

51

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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Valtrex

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

53

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

55

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

57

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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VALTREX DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH]

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Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anogenital: Pertaining to the anus and external genitals. [EU] Anomalies: Birth defects; abnormalities. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form

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salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH]

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Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH]

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Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense

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mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH]

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Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Extracellular: Outside a cell or cells. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Genital: Pertaining to the genitalia. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids

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(steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Simplex Encephalitis: An inflammatory disease of the skin or mucous membrane characterized by the formation of clusters of small vesicles. [NIH] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH]

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Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Interindividual: Occurring between two or more individuals. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually

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by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH]

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Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]

Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH]

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Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of

Dictionary 71

proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH]

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Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prophylaxis: An attempt to prevent disease. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH]

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Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the

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one sought to be benefited by its administration. [EU] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other

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disease or abnormality. [EU] Substrate: A substance upon which an enzyme acts. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Systemic: Affecting the entire body. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Varicella: Chicken pox. [EU]

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Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Virus Shedding: The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Virus shedding is an important means of vertical transmission (disease transmission, vertical). [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH]

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INDEX A Abdominal, 59, 70, 71 Acyclovir, 4, 6, 7, 9, 10, 11, 12, 14, 15, 16, 22, 24, 25, 26, 30, 31, 59, 65 Adverse Effect, 59, 73 Affinity, 59, 74 Algorithms, 59, 61 Allogeneic, 11, 14, 59 Allogeneic bone marrow transplantation, 11, 59 Allograft, 12, 59 Allylamine, 59 Alternative medicine, 34, 59 Amine, 30, 59 Amino Acid Sequence, 59, 60 Amino Acids, 59, 60, 70, 71, 72 Ammonia, 59, 60 Analog, 30, 59, 60, 65 Anatomical, 60, 67, 73 Anogenital, 24, 25, 60 Anomalies, 60, 69 Antibiotic, 4, 60, 70 Antibodies, 24, 60, 71 Antibody, 4, 59, 60, 67 Antigen, 59, 60, 67 Anti-inflammatory, 60, 66, 71 Antimetabolite, 59, 60 Antiviral, 7, 16, 23, 30, 31, 59, 60, 71 Anus, 23, 60, 61 Arteries, 60, 61, 63, 69 Asymptomatic, 3, 60 Atypical, 60, 67 Autologous, 7, 10, 60 Autologous bone marrow transplantation, 7, 60 B Bacteria, 60, 73, 75 Base, 60, 67 Bioavailability, 7, 9, 26, 61 Biopsy, 48, 61 Biotechnology, 5, 34, 43, 61 Blood pressure, 61, 74 Blood vessel, 61, 68, 74, 75, 76 Body Fluids, 61, 74 Bone Marrow, 7, 11, 14, 16, 22, 60, 61, 63, 66, 68, 69, 74 Bone Marrow Transplantation, 7, 14, 16, 22, 61

Bone scan, 61, 73 Bowel, 61, 63, 67, 71 Bowel Movement, 61, 63 Branch, 55, 61, 64, 68, 70, 74, 75 C Carotene, 61, 73 Cell, 7, 9, 10, 23, 60, 61, 65, 67, 69, 72, 76 Cell Transplantation, 23, 61 Central Nervous System, 4, 61, 65 Cerebrospinal, 6, 62 Cerebrospinal fluid, 6, 62 Chemotherapy, 6, 9, 11, 62 Chronic, 6, 26, 62, 63, 64, 67, 68, 74 Chronic Fatigue Syndrome, 6, 62 CIS, 62, 73 Clinical study, 62 Clinical trial, 4, 21, 26, 43, 62, 63, 69, 72 Cloning, 61, 62 Computational Biology, 43, 62 Computed tomography, 62, 73 Computerized axial tomography, 62, 73 Cones, 62, 73 Congestion, 62, 65 Connective Tissue, 61, 62, 65, 68 Contraindications, ii, 62 Controlled clinical trial, 7, 62 Cornea, 62, 76 Coronary, 63, 69 Coronary Thrombosis, 63, 69 Cortisone, 63, 71 Curative, 63, 75 Cyclosporine, 49, 63 Cytomegalovirus, 6, 11, 12, 14, 15, 16, 23, 24, 63, 65 Cytomegalovirus Infections, 24, 63, 65 D Databases, Bibliographic, 43, 63 Diagnostic procedure, 29, 34, 63 Dialyzer, 63, 66 Digestion, 61, 63, 67, 68, 74 Digestive system, 27, 63, 69 Direct, iii, 8, 37, 63, 72 Disease Progression, 5, 63 Disease Transmission, 63, 76 Disease Transmission, Vertical, 63, 76 Dissociation, 59, 63, 67 Dorsal, 64, 65 Drug Interactions, 38, 64

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Drug Tolerance, 64, 75 Dura mater, 64, 69, 70 E Efficacy, 14, 15, 16, 22, 24, 25, 64 Electrolyte, 64, 74 Electrons, 61, 64, 67, 72 Electrophysiological, 64, 76 Encephalitis, 22, 48, 64 Encephalitis, Viral, 64 End-stage renal, 15, 64 Environmental Health, 42, 44, 64 Enzymatic, 61, 64, 73 Enzyme, 64, 75 Epidermis, 65, 72 Epithelium, 65, 76 Erythema, 12, 48, 65 Erythema Multiforme, 12, 48, 65 Erythrocytes, 61, 65 Esophagus, 63, 65, 74 Extracellular, 62, 65, 74 F Facial, 13, 15, 65 Family Planning, 43, 65 Fat, 61, 65, 74 Fatigue, 62, 65 Fibrosis, 59, 65, 73 Fold, 26, 65 G Gallbladder, 59, 63, 65 Ganciclovir, 6, 8, 11, 65 Ganglia, 65, 70, 71 Ganglion, 65, 76 Gene, 8, 13, 61, 65 Genital, 6, 7, 10, 13, 14, 15, 23, 25, 65, 76 Gland, 63, 65, 68, 70 Glucocorticoid, 65, 71 Governing Board, 66, 71 Gp120, 66, 71 Graft, 66, 69 Graft-versus-host disease, 66, 69 Granulocytes, 66, 76 Growth, 66, 75 H Heart Transplantation, 15, 66 Hemodialysis, 9, 63, 66, 68 Hemorrhage, 66, 72, 74 Hepatitis, 66, 67 Hepatomegaly, 66, 67 Heredity, 65, 66 Herpes, 3, 4, 6, 7, 10, 12, 13, 14, 15, 16, 20, 21, 22, 23, 24, 25, 26, 30, 31, 33, 34, 48, 59, 66

Herpes Simplex Encephalitis, 22, 66 Herpes virus, 22, 48, 66 Herpes Zoster, 7, 13, 15, 21, 22, 66 Hydrogen, 59, 61, 66 I Id, 20, 49, 54, 56, 66 Immune response, 5, 60, 63, 66, 76 Immune system, 22, 24, 66, 67, 75, 76 Immunocompromised, 7, 21, 22, 67 Immunodeficiency, 11, 14, 67 Immunologic, 21, 24, 67 Impairment, 67, 69 Infarction, 63, 67, 69 Infection, 4, 7, 12, 14, 15, 22, 23, 63, 64, 67, 68, 70, 74, 76 Infectious Mononucleosis, 23, 67, 69 Infiltration, 67, 76 Inflammation, 60, 64, 65, 66, 67, 69, 70, 74 Interindividual, 9, 67 Intermittent, 67, 71 Intestinal, 8, 9, 17, 61, 67, 76 Intestine, 8, 61, 67, 68 Intracellular, 67, 76 Intravenous, 10, 11, 49, 67 Ionization, 8, 67 Ions, 61, 63, 64, 66, 67 K Kb, 42, 67 Kidney Failure, 64, 67 Kidney Transplantation, 14, 68 L Large Intestine, 63, 67, 68, 72 Leukocytes, 61, 66, 68, 69, 70 Leukopenia, 11, 68 Leukoplakia, 8, 68 Library Services, 54, 68 Liver, 59, 63, 65, 66, 68, 71, 73 Liver scan, 68, 73 Localized, 67, 68 Lymph, 24, 67, 68 Lymph node, 24, 68 Lymphadenopathy, 67, 68 Lymphatic, 67, 68, 74 Lymphatic system, 68, 74 Lymphoid, 60, 68 Lytic, 68, 73 M Magnetic Resonance Imaging, 68, 73 MEDLINE, 43, 68 Membrane, 63, 65, 66, 68, 73 Meninges, 61, 64, 68, 69 Meningitis, 7, 69

Index 79

Mental Disorders, 27, 69 Metabolite, 69, 71 MI, 57, 69 Mitochondrial Swelling, 69 Modification, 69, 72 Molecular, 43, 45, 61, 62, 69 Monocytes, 68, 69 Mononuclear, 67, 69 Mononucleosis, 24, 69 Mucositis, 7, 11, 69 Multicenter Studies, 5, 9, 69 Multicenter study, 69 Mycophenolate mofetil, 6, 69 Myocardium, 69 N NCI, 1, 23, 26, 41, 62, 69 Necrosis, 10, 67, 69 Need, 3, 50, 69, 75 Nerve, 65, 69, 70, 73, 76 Nervous System, 22, 61, 69, 70, 71 Neurotoxicity, 9, 15, 70 Neutropenia, 6, 70 Neutrophils, 66, 68, 70 Nitrogen, 59, 70 Nuclear, 64, 65, 69, 70 Nucleic acid, 70, 76 O Opsin, 70, 73 Organ Transplantation, 6, 16, 70 Outpatient, 13, 70 P Pachymeningitis, 69, 70 Palliative, 70, 75 Palsy, 10, 70 Pancreas, 59, 63, 70 Particle, 70, 76 Patch, 68, 70 Pathogenesis, 3, 70 Pathologic, 61, 63, 70 Patient Education, 48, 52, 54, 57, 70 Penicillin, 70, 75 Peptide, 8, 9, 17, 70, 71, 72 Peptide T, 8, 9, 17, 71 Peripheral Nervous System, 70, 71 Peritoneal, 9, 15, 71 Peritoneal Cavity, 71 Peritoneal Dialysis, 9, 15, 71 Peritoneum, 71 Pharmacokinetic, 8, 9, 16, 21, 26, 71 Pharmacologic, 71, 75 Pigments, 61, 71, 73 Plasma, 60, 67, 71

Plasma cells, 60, 71 Practice Guidelines, 44, 71 Precursor, 64, 71, 75 Prednisolone, 71 Prednisone, 10, 71 Prodrug, 8, 15, 25, 30, 71 Progressive, 64, 66, 69, 72 Prophylaxis, 6, 11, 12, 13, 14, 15, 16, 30, 31, 72 Protein S, 61, 72 Proteins, 59, 60, 70, 71, 72, 73, 75, 76 Protocol, 5, 24, 72 Public Policy, 43, 72 Publishing, 5, 72 Purpura, 15, 72 Q Quality of Life, 22, 24, 72 R Radiation, 72, 73, 76 Radioactive, 61, 66, 67, 68, 70, 72, 73 Randomized, 5, 6, 7, 9, 10, 11, 13, 15, 21, 23, 64, 72 Randomized clinical trial, 13, 72 Reactivation, 11, 12, 15, 16, 22, 72 Receptor, 60, 66, 71, 72 Rectum, 60, 61, 63, 68, 72 Recurrence, 15, 72 Refer, 1, 66, 69, 72 Regimen, 64, 72 Remission, 72 Restoration, 72, 73 Retina, 10, 62, 73 Retinal, 10, 73 Retinol, 73 Retrospective, 14, 73 Risk factor, 25, 73 Rods, 73 S Salivary, 63, 73 Salivary glands, 63, 73 Scans, 5, 73 Sclerosis, 4, 73 Screening, 62, 73 Septic, 7, 73 Sequence Homology, 71, 73 Serologic, 25, 73 Serum, 4, 6, 73 Shedding, 73, 76 Side effect, 22, 37, 59, 73, 75 Social Environment, 72, 74 Sodium, 31, 74 Soft tissue, 61, 74

80

Valtrex

Solid tumor, 13, 74 Specialist, 49, 74 Species, 59, 61, 63, 70, 73, 74, 75 Spinal cord, 61, 62, 64, 65, 68, 70, 71, 74 Spleen, 63, 68, 74 Splenomegaly, 67, 74 Staging, 73, 74 Stem cell transplantation, 14, 23, 74 Stem Cells, 59, 66, 74 Steroids, 13, 49, 66, 74 Stimulant, 74, 75 Stomach, 59, 63, 65, 71, 74 Stroke, 27, 42, 74 Subacute, 67, 74 Subclinical, 67, 74 Substrate, 12, 17, 75 Suppression, 10, 14, 24, 75 Suppressive, 10, 75 Survival Rate, 22, 75 Systemic, 13, 38, 61, 67, 71, 75 T Therapeutics, 8, 9, 30, 31, 38, 75 Threonine, 71, 75 Thrombosis, 72, 74, 75 Tissue, 4, 59, 60, 61, 62, 64, 66, 67, 68, 69, 71, 73, 74, 75 Tolerance, 26, 75 Toxic, iv, 75 Toxicity, 64, 75

Toxicology, 44, 75 Toxins, 60, 64, 67, 75 Transfection, 61, 75 Transplantation, 6, 8, 10, 12, 14, 15, 16, 75 Trauma, 69, 75 U Unconscious, 66, 75 V Vaccine, 72, 75 Valine, 30, 31, 75 Varicella, 25, 26, 75 Vascular, 59, 67, 76 Vein, 67, 70, 76 Ventricle, 76 Ventricular, 6, 76 Ventricular Function, 6, 76 Vesicular, 66, 76 Veterinary Medicine, 43, 76 Viral, 4, 30, 31, 48, 64, 76 Virus, 3, 4, 6, 7, 8, 10, 11, 13, 14, 15, 16, 23, 26, 49, 66, 67, 76 Virus Replication, 8, 76 Virus Shedding, 3, 76 W White blood cell, 23, 60, 67, 68, 70, 71, 76 X X-ray, 62, 70, 73, 76 Z Zoster, 15, 25, 26, 76

Index 81

82

Valtrex

Index 83

84

Valtrex

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